This program is aimed at ultimate palliation of the two most prevalent diseases of human hemoglobin: those involving sickle hemoglobin (Hb S), and the thalassemia syndromes. The intended mechanism of palliation is increased net synthesis of fetal hemoglobin (Hb F), to be achieved by augmentation of gamma-globin synthesis. There are two specific aims. The first is to test our hypothesis that persistent synthesis of Hb F in the Hb S syndromes is caused by an abnormality in translation of messenger RNA (mRNA) for Beta S globin chains, thus reducing the relative availability of Beta S chains for Hb S synthesis and at the same time increasing the relative availability of gamma chains for Hb F synthesis. Cell-free systems capable of either globin or hemoglobin synthesis will be combined in experiments designed to test this hypothsis. The second specific aim is to examine broader concepts of genetic control of hemogobin synthesis, with the hamster as an experimental animal model bearing a fetal hemoglobin fraction into adult life. Hormones suspected of exercising partial control of hemoglobin synthesis will be tested in adult hamsters and in preparations of hamster fetal liver erythroid cells. Relative rates of synthesis of adult and fetal hemoglobins will be examined, and evidence for altered relative rates will be pursued in erythroid cell suspensions. Assays for hormone influence in vitro will include measurements of rates of synthesis of globin and hemoglobin, and characterization of nuclear non-histone protein, a possible regulator of gene activition. The ultimate clinical goal is control of hemoglobin synthesis in human disease states.